Rapid and sensitive biosensing of nucleic acids or proteins is vital for the identification of pathogenic agents of biomedical and bioterrorist importance, providing forensic evidence, and for diagnoses of genetic diseases, among other uses. Development of methods that do not require target-amplification systems like polymerase chain reaction (PCR) that increase the complexity of the determination and the potential for error are a major challenge. Surface-enhanced Raman scattering to detect a silver coating built up on patches of several thousand immobilized target DNA molecules bound to gold nanoparticles has been used to detect target DNA at concentrations as low as 20 femtomolar, and is among the most sensitive means to detect DNA (ref (3-6)). However, these methods are limited by nonspecific binding, hybridization kinetics, and extensive incubation times. These technologies all require the binding of several thousand DNA-bound reporter groups as an aggregate to obtain a detectable signal. The ultimate goal is to achieve a detectable signal for each DNA molecule. Detection of a molecule with a specific sequence necessarily depends upon hybridization of the target with a probe DNA molecule, and upon the target-dependent assembly of a molecular detection probe such as a nanoparticle. Consequently, with single molecule biosensing, the detection limit becomes dependent on the statistical difference between target-specific and nonspecific binding events.